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Administrative data

Description of key information

Acute studies are available by oral and dermal route and showed no death at the maximal dose of 2000 mg/kg.
No data is available by inhalation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 January 2014 -- 26 March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 209 g (range: 194 g to 234 g)
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 24 February 2014 to 26 March 2014
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: following recommendation from the Sponsor, the solubility assay first started at the concentration of 200 mg/mL, and following indication on the test article description, the choice vehicle was corn oil.

- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION (if unusual): fresh dose formulations were prepared by the CiToxLAB France Pharmacy on the day of each administration and kept at room temperature and protected from light prior to administration.



CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: ----
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
Three nulliparous and non-pregnant female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
no
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 other: mg/kg
Based on:
test mat.
Remarks on result:
other: no mortality
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
No clinical signs were observed in any animals.
Body weight:
When compared to CiToxLAB France historical control data, a lower body weight gain was noted in 2/6 females (groups 2 and group 3) given 2000 mg/kg (+7 g vs. +20 g ± 6.7 g in control data base) between Day 8 and Day 15. A higher body weight gain was observed in one female (group 3) (+30 g vs. +20 g ± 6.7 g in control data base) given 2000 mg/kg over the same period.
Nevertheless, compared to CiToxLAB France historical control data, the body weight of the animals was considered to be unaffected by the test item treatment. (see Table 1)
Gross pathology:
There were no test item-related macroscopic post-mortem findings.
The few gross abnormalities were considered to be part of the normal background in untreated rats of these strain and age.
Other findings:
no

 Table 1

Sex

Female

Group

CiToxLAB France historical control data

1

2

3

Dose-level (mg/kg)

0

300

2000

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

198 (± 6.6)

201 (± 6.2)

224 (± 13.2)

201 (± 5.3)

. Day 8

239 (± 8.6)

246 (± 10.0)

273 (± 13.7)

242 (± 9.5)

. Day 15

258 (± 8.6)

262 (± 8.7)

285 (± 14.0)

261 (± 20.0)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+41 (± 7.2)

+45 (± 6.1)

+48 (± 0.6)

+41 (± 4.7)

. Days 8-15

+20 (± 6.7)

+16 (± 2.5)

+12 (± 4.7)

+19 (± 11.5)

. Days 1-15

+60 (± 6.0)

+61 (± 4.4)

+61 (± 4.0)

+60 (± 14.7)

SD: standard deviations.

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP Regulation
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test item, was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as harmful or toxic by oral route according to the criteria of the CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item, following a single oral administration (gavage) to rats.

This study was conducted in compliance with OECD Guideline No. 423 and the principles of Good Laboratory Practices.

Methods

The test item, was administered once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage‑volume of 10 mL/kg. The test item was prepared in corn oil.

Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data have been taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons. After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as no toxicity was observed at this higher dose-level, the results were confirmed in other three females.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study report as no microscopic examination was performed.

Results

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals.

When compared to the historical control data, a lower body weight gain was noted in 2/6 females given 2000 mg/kg (+7 gvs.+20 g ± 6.7 g in control data base) between Day 8 and Day 15. A higher body weight gain was observed in 1/6 females (+30 g vs.+20 g ± 6.7 g in control data base) given 2000 mg/kg over the same period.

Nevertheless, compared to the historical control data, the body weight of the animals was considered to be unaffected by the test item treatment.

No test item-related macroscopic post-mortem findings were noted.

Conclusion

Under the experimental conditions of this study, the oral LD50 of the test item, was higher than 2000 mg/kg in rats.

Therefore, the test item should not be classified as harmful or toxic by oral route according to the criteria of the CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The acute oral study is considered to be reliable.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 January 2014 -- 21 March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 348 g (range: 341 g to 361 g) for the males and 235 g (219 g to 254 g) for the females
- Housing: polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 04 March 2014 to 21 March 2014
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no
Duration of exposure:
24 hr
Doses:
2000 mg/kg
No. of animals per sex per dose:
Ten rats (five males and five nulliparous and non pregnant females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment, on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality
Mortality:
No unscheduled deaths occurred during the study.

Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
A very slight to moderate-to-severe erythema was noted in all males and a very slight to well defined erythema was recorded in all females from Day 2 until Day 6 at the latest. This was associated with very slight to moderate dryness from Day 4 or 5 until Day 13 at the latest in all animals. Scabs were observed in 2/5 males from Day 7 to Day 11.
Body weight:
When compared to historical control data, a higher body weight gain was observed in one male (+57 g vs. +39 ± 11.5 g in control data base) between Days 1 and 8 whereas a lower body weight gain was noted in two males (+35 g and +33 g, respectively, vs. +50 ± 12.0 g in control data base) between Day 8 and Day 15.
A lower body weight gain was observed in two females (+13 g and +14 g, respectively, vs. +25 ± 10.0 g in control data base) between Days 1 and 8. This was followed by a body weight loss of 2 g in one female over the second part of the observation period.
Nevertheless and in absence of marked body weight effect, body weight of animals was considered unaffected by the test item treatment in both sexes when compared to historical control data.
Gross pathology:
The spleen was enlarged in 4/5 males given the test item at 2000 mg/kg. In the absence of macroscopic findings in females given the same dose-level, this finding was considered to be incidental and unrelated to the test item administration.
Other findings:
no
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP Regulation
Conclusions:
Under the experimental conditions of this study, the dermal LD50 of the test item, was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as acutely toxic by dermal route according to the criteria of the CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item, following a single dermal application to rats.

This study was conducted in compliance with OECD Guideline No. 402 and the principles of Good Laboratory Practices.

 

Methods

The test item was applied in its original form to the skin of five female then five male Sprague‑Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi‑occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From Day 2, any local reactions at the treatment site were also noted. Body weight was recorded on Day 1 and then on Days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.Macroscopic lesions were preserved in buffered formal in then destroyed at the finalization of the study report as no microscopic examination was performed.

 

Results

No unscheduled deaths occurred during the study.

No clinical signs indicative of systemic toxicity were observed in any animals.

A very slight to moderate-to-severe erythema was noted in all males and a very slight to well‑defined erythema was recorded in all females from Day 2 until Day 6. This was associated with very slight to moderate dryness from Day 4 or 5 until Day 13 in all animals. Scabs were observed in 2/5 males from Day 7 to Day 11.

When compared to CiToxLAB France historical control data, a higher body weight gain was observed in 1/5 males (+57 g vs. +39 ± 11.5 g in control data base) between Days 1 and 8 whereas a lower body weight gain was noted in 2/5 males (+35 g and +33 g, respectively, vs. +50 ± 12.0 g in control data base) between Day 8 and Day 15.

A lower body weight gain was observed in 2/5 females (+13 g and +14 g, respectively, vs. +25 ± 10.0 g in control data base) between Days 1 and 8. This was followed by a body weight loss of 2 g in one of them over the second part of the observation period.

Nevertheless and in absence of marked body weight effect, body weight of animals was considered unaffected by the test item treatment in both sexes when compared to CiToxLAB France historical control data.

At the end of the observation period, there were no macroscopic findings at necropsy attributable to the test item administration.

 

Conclusion

Under the experimental conditions of this study, the dermal LD50 of the test item, was higher than 2000 mg/kg in rats.

 

Therefore, the test item should not be classified as acutely toxic by dermal route according to the criteria of the CLP Regulation.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The acute dermal study is considered to be reliable.

Additional information

Acute oral study (Papineau 2014)

The objective of this study was to evaluate the potential acute toxicity of the test item, following a single oral administration (gavage) to rats (OECD guideline 423). The test item, was administered once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage‑volume of 10 mL/kg. The test item was prepared in corn oil.

Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data have been taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons. After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as no toxicity was observed at this higher dose-level, the results were confirmed in other three females. Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15.

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals.

When compared to the historical control data, a lower body weight gain was noted in 2/6 females given 2000 mg/kg (+7 g vs.+20 g ± 6.7 g in control data base) between Day 8 and Day 15. A higher body weight gain was observed in 1/6 females (+30 g vs.+20 g ± 6.7 g in control data base) given 2000 mg/kg over the same period.

Nevertheless,compared to the historical control data, the body weight of the animals was considered to be unaffected by the test item treatment.

No test item-related macroscopic post-mortem findings were noted.

Under the experimental conditions of this study, the oral LD50 of the test item, was higher than 2000 mg/kg in rats.

Acute dermal study (Papineau 2014)

The objective of this study was to evaluate the potential toxicity of the test item, following a single dermal application to rats (OECD guidelaine 402).

The test item was applied in its original form to the skin of five female then five male Sprague‑Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi‑occlusive dressing for 24 hours.

No unscheduled deaths occurred during the study. No clinical signs indicative of systemic toxicity were observed in any animals. A very slight to moderate-to-severe erythema was noted in all males and a very slight to well‑defined erythema was recorded in all females from Day 2 until Day 6. This was associated with very slight to moderate dryness from Day 4 or 5 until Day 13 in all animals. Scabs were observed in 2/5 males from Day 7 to Day 11.

When compared to historical control data, a higher body weight gain was observed in 1/5 males (+57 g vs.+39 ± 11.5 g in control data base) between Days 1 and 8 whereas a lower body weight gain was noted in 2/5 males (+35 g and +33 g, respectively,vs.+50 ± 12.0 g in control data base) between Day 8 and Day 15. A lower body weight gain was observed in 2/5 females (+13 g and +14 g, respectively,vs.+25 ± 10.0 g in control data base) between Days 1 and 8. This was followed by a body weight loss of 2 g in one of them over the second part of the observation period.

Nevertheless and in absence of marked body weight effect,body weight of animals was considered unaffected by the test item treatment in both sexes when compared to historical control data.

At the end of the observation period, there were no macroscopic findings at necropsy attributable to the test item administration.

Under the experimental conditions of this study, the dermal LD5of the test item, was higher than 2000 mg/kg in rats.

 


Justification for selection of acute toxicity – oral endpoint
Only one study is available in acute toxicity by oral route.

Justification for selection of acute toxicity – dermal endpoint
Only one study is available in acute toxicity by dermal route.

Justification for classification or non-classification

Based on the available data, Tricyclodecane dimethanol diacrylate is not classified in the acute toxicity endpoint according to the Regulation EC 1272/2008 and the Directive 67/548/EEC.